In Vitro w/ Genetic Testing – Experiences?

FI and I aren’t planning on TTC for at least a couple more years, but we’ve already made up our minds that we will most likely go the in vitro route in order to have the option of pre-implantation genetic testing. I’m a carrier for an x-linked genetic disease (50/50 chance of passing it on to our kids), and we’d rather not make that gamble. I’m just wondering if anyone else on the bee has had a similar experience. In my research, I’ve found plenty of personal accounts of in vitro, but they’ve all been from the perspective of overcoming infertility. Have any of you conceived through in vitro to avoid passing on a genetic disease? If so, what was the experience like? Did it still take several tries as it usually does for women struggling with fertility? How long did the process take, and how did you prepare for it? Were family and friends supportive of the decision?

Not nosey at all! It depends on what you count as “passing the disease” I suppose. You’re correct that the odds of one of my children expressing the disease is 25%, but my overall chances of passing on the gene is 50%. If I have a boy, he will either have the disease, or he won’t, 50/50, period. If I have a girl, she has a 50% chance of being a carrier like me and being in the same predicament when she has children. Our hope is that we can end it with my generation. 🙂

LadyAna: I haven’t experienced it but a friend is going through the process at the moment. Not that I know the details but I know she started the process close to the beginning of the year and did her first IVF recently. Unfortunately it wasn’t successful and she’s looking into doing her second one soon.

My family is riddled with fragile x (my mother is a carrier) and I was prepared to have to go this route. There are actually support threads out there for PGD which is what we were going to use if I ended up being a carrier. I was not, but we did a lot of research. Not to send you somewhere else, but there were a TON of people on BabyCenter who knew a lot about this. They were super helpful.

I’m in my second cycle of IVF with PGD for Fragile X and male factor, I have 50/50 odds of passing my bad chromosome and having my permutation expand into a full mutation. Unlike some families, mine has no history of Fragile X, developmental disabilities, autism, fertility problems or any other markers that could have clued us in to me being a carrier. We found out when DH’s geneticist decided to test me because of my crappy hormone levels while running DH’s MFI tests. I also have the unfortunate FXPOI that goes along with some premutation carriers so we don’t get a ton of embryos from each cycle. Because of that, we’re batching our embryos from two cycles so we can do PGD on them all at once – we’re paying out of pocket for IVF but our insurance will cover PGD so we need as many as possible to test. Two cycles is running us about $40,000.

We’re doing our IVF cycles back to back, our first cycle resulted in 4 frozen embryos and we’re hoping to get at least that many in our second. IVF with PGD is very different from traditional IVF – you need to make sure you pick a clinic and doctor that has TONS, not some, but TONS of experience with PGD and the biopsy process. You do not want to be the client they use to get some experience. How many PGD cases do they do a year? How many biopsies? Do they biopsy day 3 or day 5? Is it done in house or do they use a traveling embryologist? How much experience do their embryologists have, they need a certain number of biopsies to be qualified and you want yours to be well over that number. Are they aware that ICSI is necessary to prevent genetic contamination for PGD? What freezing process do they use and what is their success rate for FET? You also need to pick a genetics lab with excellent statistics for results to build your probe, you don’t want inconclusives.

I’m in several PGD/genetics groups and from what I’ve seen it does often take several cycles to get your healthy embryos, even if you have no fertility problems. IVF recruits eggs your body wouldn’t otherwise use that month so you end up pulling eggs with other issues like chromosomal abnormalities as well. You may want to add on aCGH testing as well, single gene PGD only looks for your mutation and doesn’t find issues like trisomy 21. This is an extra expense but I think DH and I are going to add it on, I’m only 27 but they still see a number of abnormal chromosomes in my age range. Factor in that some embryos will be affected by the disease and there are some women in my support group who are on their 10<sup>th</sup> cycle! Others get lucky on the first try, I think it all depends on the person. That said, DH and I can only afford two cycles so we’re putting all our eggs in this basket, hoping we get some normals to transfer, and hoping we’re some of the lucky ones who get our take home baby from our first FET.

As for family, I would have preferred not to share our infertility journey with them but we needed their saliva to build the probe. They’ve been supportive but its very uncomfortable for me to have them asking over and over about our progress and what we’re doing now. The process takes a long time, you need to pick a clinic, go through all your precycle testing, it takes on average about 6-8 weeks to build a probe depending on the genetics lab, and then you have the cycles themselves. Getting our insurance to approve our PGD coverage also took forever. You’re going to be injecting a lot of hormones into your body, I do 4 shots a day for my cycle, and getting transvaginal ultrasounds every other day so it can be a lot to deal with. For me, my family’s repeated questions feel intrusive and annoying even though I know that’s not their intention.

I will also say that you should seriously consider doing acupuncture before and during your IVF cycles. I started off with IUIs and acupuncture dramatically improved my results each cycle. First IUI was 1 follicle, second was 7 follies, and first IVF was 14 follies which yielded 11 eggs that turned into 4 day 5 embryos. I was told I’d never make more than 3 so we are over the moon. This also means I had several months of acupuncture under my belt before we got to the IVF process. Acupuncture also helps balance your hormones so I don’t feel like a crazy PMS lady during my IVF cycles and it helped a ton with my recovery from my egg retrieval. I go once a week with an extra appointment before each egg retrieval and I will go for extra appointments before and after my FET.

Sorry this is such a novel, IVF with PGD is a really unique process and it took me a long time figure out what was important and what questions I needed to ask. I hope you have lots of luck when you’re ready to try 🙂

ETA: I don’t know how old you are, but the younger you start the better. The younger you are, the more eggs you’ll make, the less chromosomally abnormal eggs you’ll have, and the better your chances are. You can always do your IVF now and keep your embryos frozen until you’re ready to transfer.

saraja87: Thank you so much for your thorough and detailed answer. I learned more from that post than any other source single sourse I’ve read so far, and hearing about your experience and the knowledge you’ve accumulated is incredibly helpful! I’ll be turning 27 in a couple months, and we think we’d like to have a first child around the time I’m 30. We definitely don’t have the money to pay for IVF right now without taking out a loan or something, but I know I need to start doing my homework now and not put it off until we’re ready to have a baby. Thanks again!

saraja87: I know I’m the only family member with the genetic mutation, would they still need saliva from other family members? Do they start with just gene testing on me? I know the gene involved, but I was diagnosed via a different blood test, and there are multiple known mutations within the gene that can cause the condition.

From what I’ve seen, the clinics here work with labs in the states for any of the genetic stuff. Do you think the time/distance would have a negative impact on the final result?

AB Bride: Usually you start with a genetics blood panel that identifies your mutation, the result is most often just a short, written report that names your specific gene mutation and it’s location. You might already have this so you’d email it to your lab. Depending on your mutation, they’ll take blood from you and your partner and then usually saliva samples from family members as a control for genes without the mutation. From my family, they took a saliva sample from my sister who has the same premutation, and a saliva sample from my mother who does Not have the mutation as a control for my healthy chromosome. My mutation was passed down from my father but he was unavailable or they would have taken a sample from him too.

Some clinics have a preference as to which lab they work with but most will work with all the biggies (Reprogenetics, RGI, Genesis, etc) and they’re usually far away. Each lab has specific criteria that an IVF clinic has to meet to be sure they’re capable of providing viable samples for testing, so it’s faster if the clinic you’re working with already has a relationship with your genetics lab because they will be prescreened. I’m in CA but my genetics lab is in New Jersey, so my biopsy samples are frozen at my IVF clinic and then shipped to them for testing. It doesn’t matter where you are as long as the frozen samples can be shipped 🙂

LadyAna: You’re welcome! I would probably start with a fertility and genetics work up and check to see what your insurance covers. Some people are lucky enough to have IVF covered which would eliminate a lot of roadblocks! Each plan is different though and they can have all sorts of qualifiers – some will only cover it if you have fertility problems, hence the work up, but often your doctor can work with you and your insurance to advocate for coverage. Since you have a known mutation, I would push hard to have your PGD covered at the very least.

saraja87: That was such a great post. LadyAna, I’m a former IVF scientist and saraja87 covered just about everything I would have said, especially in choosing a clinic that does a LOT of PGD every week, even if it means you have to do some travelling. You can always have your excess frozen embryos shipped to a local clinic later for subsequent frozen-thawed transfers. From experience I can assure you that you need to be doing this every week or so, or your skills are just not as good as they should be. It’s super-fiddly and super-precise and the margin for error is miniscule. I’d ask to have a meeting with the scientist doing the PGD and I’d ask him/her specifically how often they were doing biopsies. This is a big decision and you want the right team on your side.

I did the actual embryo biopsies in our lab, where I removed a cell and fixed it on to the slide then sent the slides on to the genetics centre for analysis. So from my side of things I can also add some information about embryo development post-biopsy.

I’m in Australia but the technology is similar to the USA. Here’s a very rough example. For a 30 year old I’d expect an average of around 12-14 eggs, of which maybe 10 would fertilize. For a non-PGD case we’d grow the embryos in the lab for 5 days to hopefully reach the blastocyst stage of development. I would expect about 3-4 good blastocysts from 10 fertilized eggs (sometimes 8, sometimes 0). It was common to see at least half of the embryos slow down or stop developing during the 5 days regardless of the type of infertility. Some genetic conditions also mean that you don’t produce as many eggs as other ladies of the same age. Every one is different, this is just a rough guide.

For PGD cases we would grow the embryos for 3 days before biopsy and would get maybe 7-8 suitable for biopsy. You would sometimes get embryos that didn’t recover after being biopsied but we have no way of knowing whether they would have stopped growing anyway and on average would still get about 3 nice blastocysts on Day 5. We would have the results the morning of Day 5 and if there was more than 1 embryo that was clear on your PGD screening then we would pick the best one (or occasionally two) for transfer and freeze the others.

Cycles normally go smoothly but like any medical procedure, things can go wrong during the biopsy. Either the embryo for some reason collapses during biopsy (rare) or sometimes we would get a “no result” or an “inconclusive result” from the testing. This was not for every case but it would happen every few cycles and I’d say about 5-10% of embryos would be like this. Normally we’d have other embryos in the cohort to work with but if that was the only embryo as sometimes happened in the 40+ age group, it was dreadful. What was worse was when all the embryos stopped growing, or when we had embryos that grew well but all got inconclusive results. It’s possible that the clinic might be able to re-biopsy at the blastocyst stage but you’d be subjecting the embryos to additional stress so it might not survive – better than no chance though.

I’m not at all familiar with your health care system but if travelling to a busy clinic is a problem you could perhaps investigate doing your cycle locally and freezing all suitable embryos, shipping them to the specialist clinic for analysis and fly up for the embryo transfer only. It’s really not ideal as you run the risk of damaging the embryos by freezing them but we had to do this occasionally for regional patients.

As I don’t know your details I can’t comment on your egg production prospects but will second what PPs are saying in that I’d go sooner rather than later. As we age, our eggs age with us and older eggs are more likely not to grow properly as embryos. Each embryo goes through many cell division cycles where the DNA inside will duplicate then split in half, and and this process is less stable with older eggs and can cause delayed or arrested development in the embryos. Guys are lucky, they get to make new sperm every day so they don’t really have the same problem!

On the subject of sperm – it’s not a good idea for your man to store up his sperm; it’s actually better to keep things ticking over and have regular ejaculation to have the best quality sperm for IVF cycles. See what your clinic guidelines are but I’d suggest 2-5 days is optimal, with 2-3 days best. Sperm don’t actually last very long once they’re produced and if they are breaking down inside his reproductive tract, the breakdown products are not good for the live sperm still there. I heard a colleage doctor say once that a patient had to “keep cleaning out the pipes” and it made me smile but stuck in my mind.

Keep in mind that it might take a few months to jump through all the hoops and get the stage where you can start your cycle. I remember one patient where it took 8 months to get the probe sorted out but that was quite a few years ago and she had a rare condition. So just keep reading as much as you can to be prepared with the right questions when you get in to start the process. What you are needing to have done is become more and more routine and technology is improving all the time. Wishing you the very best of luck.

AussieEncore: Thank you for adding in more info! It’s so helpful to hear from someone who actually works with the embryos 🙂 You’re completely right, we actually picked our clinic based on their embryologist – we met with him specifically and he gave us a (from a distance, got to keep things sterile!) tour of their embryology lab. My clinic does over 500 PGD cases a year and the embryologist we spoke to biopsies 3 embryos a day on average. He’s only one of several embryologists on staff and we liked him so much that he made the final decision for us.

I also wanted to add that in the states, most clinics now do day 5 biopsies with a FET instead of a fresh transfer. The idea is to weed out the embryos that would have arrested before the blastocyst stage and more importantly, to have a differentiated target to biopsy so you can get a few more cells. Here day 5 biopsies are much less likely to have inconclusive results, issues with mosaicism or instances of damage to the embryo. I’m sure there’s also a monetary component as well since most people pay out of pocket and after a certain number, pay per embryo for PGD. Usually a genetics lab will test say up to 8 samples and anything after that is extra. Many clinics also have better stastics with FET instead of fresh transfers now that they use vitrification and you can ensure an optimal uterine environment for transfer.